A COMPARISON OF LIPOPOLYSACCHARIDE-INDUCED HEPATITIS IN ETHANOL-FED WISTAR AND LEWIS RATS

Elevated concentrations of plasma proinflammatory cytokines have been detected in patients with alcoholic hepatitis (AH) and in a model of l ipopolysaccharide-induced hepatitis in ethanol-fed Wistar rats. These cytokines have been implicated in the pathogenesis of the liver damage . Considering the likely involvement of the immune system in AH, and t he frequent use of Lewis rats in autoimmune disease models, Lewis rats were examined in the model to determine whether they would more close ly mimic the immune status of a chronic alcoholic and be a preferable strain for use in future experiments. Lipopolysaccharide-induced hepat ic tumor necrosis factor-cu, interleukin-1 alpha, interleukin-1 beta, and interleukin-6 mRNA expression was examined in both rat strains. Th e overall pattern of histological (panlobular piecemeal necrosis) and biochemical liver damage (plasma ALT levels), and cytokine expression was similar in both strains. Thus, it would appear that, despite the k nown susceptibility of Lewis rats to autoimmune phenomena, they do not respond to the experimental regime significantly better than Wistar r ats. This study confirms that unknown mediators are contributing to th e liver damage seen in this model and possibly in AH.